Influenza A viruses (IAV) are a high threat to humanity because of a lack of proper effective antiviral drugs and resistance of viruses to existing vaccines. We describe the sufficient anti-IAV effect of Ans/PL-Dz nanocomposites that contain deoxyribozymes (Dz) immobilized on anatase TiO2 nanoparticles (Ans) through polylysine linker (PL). The Dz-containing nanocomposites appear to be more efficient than the Ans/PL-ODN nanocomposites that contain common oligodeoxyribonucleotides (ODN) targeted to the same RNA regions of the viral genome. The simultaneous use of nanocomposites that contain Dz and ODN, which are targeted to different sites of viral RNA provides a higher overall effect than the independent action of each of them (synergism). The inhibition of IAV with the proposed nanocomposites was shown to be effective, sequence-specific, and dose-dependent. The most efficient Ans/PL-Dz nanocomposite exhibited a high antiviral effect in vivo on mice models. The efficiency of IAV inhibition with this nanocomposite in vitro and in vivo is higher than that for the approved antiflu drug oseltamivir. The results open the prospect of creating a unique antiviral agent suitable for IAV suppression.

The antiviral activity of aqueous and ethanol extracts from the fruiting bodies of gasteroid Basidiomy-cetes of Western Siberia: Lycoperdon pyriforme, Lycoperdon perlatum, and Phallus impudicus, as well as an aqueous extract from cultivated mycelium of P. impudicus and total polysaccharides from it, on MDCK cell culture against influenza A virus, was studied. Aqueous and ethanol extracts from the fruiting bodies of all studied gasteroid fungi showed antiviral activity against human influenza virus A/Aichi/2/68 (H3N2) and bird A/chicken/Kurgan/05/2005 virus (H5N1). At the same time, extracts from P. impudicus and L. pyriforme showed more pronouncing antiviral activity compared to the activity of the reference drug Tamiflu against the A/H5N1 avian influenza virus. A high antiviral efficacy of an aqueous extract from cultivated mycelium of the P. impudicus and a sample of total polysaccharides from this extract against the A/H5N1 avian influenza virus was revealed.

Представлены сравнительные данные фитохимической оценки содержания биологически активных веществ, проявления антирадикальной активности и противовирусных свойств в растительном сырье Astragalus glycyphyllоs L. из дикорастущих популяций лесостепной зоны Западной Сибири. В течение вегетационного периода исследована динамика и показаны особенности накопления общего содержания фенольных соединений, флавоноидов, танинов, фенолокислот, сапонинов, каротиноидов, хлорофиллов а и b, пектинов и протопектинов, изменение антирадикальной активности и противовирусного действия в отношении вируса гриппа человека - A/Aichi/2/68 (H3N2) и птиц - A/chicken/Kurgan/05/2005 (H5N1) в экстрактах, полученных из растительного сырья надземной и подземной частей A. glycyphyllоs. Установлено, что содержание БАВ надземной части A. glycyphyllоs богаче, чем подземной. В надземной части A. glycyphyllоs накапливаются максимальные количества большинства биологически активных веществ исследуемых групп в разные фазы развития, но, в основном, в фазе окончания плодоношения. В подземной части в максимальных количествах найдены только протопектины - в фазах начала вегетации и плодоношения. Антирадикальная активность экстрактов из надземных и подземных частей A. glycyphyllоs проявлялась в течение всего вегетационного периода, но более эффективными оказались образцы из сырья надземной и подземной частей в конце вегетации. Исследование токсичности и противовирусного действия экстрактов, полученных из сырья обеих частей A. glycyphyllоs в максимально переносимых концентрациях показало, что индекс нейтрализации экстрактов находился в пределах от 0 до 1.5 lg, в зависимости от субтипа вируса гриппа А, периода вегетации A. glycyphyllоs, его части в исследовании и типа экстракта. По сравнению с контролем, отмечается достоверное снижение инфекционности вируса гриппа человека и вируса гриппа птиц под действием экстрактов A. glycyphyllоs. Comparative data of phytochemical evaluation of the content of biologically active substances, antiradical activity and antiviral properties in plant raw materials of Astragalus glycyphyllos L. from wild populations of the forest-steppe zone of Western Siberia are presented. During the vegetation period the dynamics of the content and the peculiarities of accumulation of the total content of phenolic compounds, flavonoids, tannins, phenolic acids, saponins, carotenoids, chlorophylls a and b, pectins and protopectins were investigated, changes in antiradical activity and antiviral action against human influenza virus - A/Aichi/2/68 (H3N2) and bird - A/chicken/Kurgan/05/2005 (H5N1) in extracts obtained from plant raw materials of above-ground and underground parts of A. glycyphyllos. It was found that the aboveground part of A. glycyphyllos is richer in BAS content than its underground part. In the aboveground part of A. glycyphyllos maximum amounts of most biologically active substances of the studied groups are accumulated in different phases of development, but mainly in the phase of fruiting termination. In the underground part, only protopectins were found in maximum amounts in the phases of the beginning of vegetation and fruiting. The antiradical activity of extracts from above-ground and underground parts of A. glycyphyllos was manifested during the whole vegetation period, but samples from raw materials of above-ground and underground parts at the end of vegetation were more effective. The study of toxicity and antiviral effect of extracts obtained from raw materials of both parts of Astragalus glycyphyllos in maximum tolerated concentrations showed that the IN of the extracts was within the range from 0 to 1.5 lg, depending on the subtype of influenza A virus, the growing season of A. glycyphyllos, its part in the study and the type of extract. Compared to the control, there was a significant decrease in the infectivity of human influenza virus and avian influenza virus under the influence of A. glycyphyllos extracts.

Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the cellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The objective of the work is to create nanocomposites consisting of TiO2 nanoparticles, antisense oligonucleotides, and photoactive groups and to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in the cellular system. Materials and methods. Influenza virus A/Aichi/2/68 (A/H3N2), N-succinimide ether of p-azidotetrafluorobenzoic acid, TiO2 nanoparticles, and oligodeoxyribonucleotides have been used in the work. The antiviral activity of the proposed nanocomposites has been studied on the MDCK cells infected with the A/H3N2 virus. Results and discussion. Unique nanocomposites have been created, which consist of three functional components, i.e., titanium dioxide nanoparticles, antisense oligonucleotides, and the photoactive tetrafluoroarylazide group, respectively, providing penetration into cells, selective interaction with target nucleic acids, and photomodification of the targets. A significant antiviral site-specific action of the nanocomposites has been demonstrated against the influenza A virus in the cellular system, which exceeds the effect of the analogous samples that contain no photoactive groups. Conclusion. The biological activity of the created nanocomposites has been demonstrated by the example of highly effective suppression of influenza A virus replication in the cellular system. The results indicate the prospects of using the proposed drugs to affect target nucleic acids inside cells.

Objective: Stability and monodispersity are important properties of nanoparticles and nanocomposites, that ensure the reliability of their application in biological systems and the reproducibility of results. The preparation of non-agglomerated oligonucleotide-containing nanocomposites based on anatase titanium dioxide nanoparticles (Ans ODN) is the aim of this study. Methods: The immobilization of oligodeoxynucleotides on TiO2 nanoparticles was studied by dynamic light scattering and transmission electron microscopy. The antiviral activity of the synthesized samples was evaluated against VERO cells infected with herpes simplex virus type 1. Results and Discussion: The effect of NaCl on the agglomeration of the nanoparticles and the nanocomposites in aqueous solutions was studied. The presence of NaCl leads to agglomeration of the nanoparticles and the nanocomposites. It was shown that the nanocomposites are formed in an aqueous solution in the absence of NaCl. A comparison of the biological activities of the nanocomposites prepared in water and in saline solution was carried out on the example of inhibition of replication of the herpes simplex virus type 1 in the cell culture. The studied nanocomposite, regardless of the preparation method (in water or in 0.9

Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the intracellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The aim of the study is to create nanocomplexes consisting of aminopropylsilanol nanoparticles and short interfering RNA (siRNA) to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in vitro. Materials and methods. MDCK cells, influenza virus A/chicken/Kurgan/05/2005 (A/H5N1), aminopropylsilanol nanoparticles, and native and modified siRNA molecules. Results and discussion. We have prepared unique Si~NH2/siRNA nanocomplexes, which consist of aminopropylsilanol nanoparticles and siRNA molecules, which enable cell penetration and selective interaction with target nucleic acids, respectively. The antiviral activity of the proposed nanocomplexes has been studied on MDCK cells infected with the influenza A/H5N1 virus. It has been shown that the double-stranded siRNA molecules in the nanocomplexes, which act by the RNA interference mechanism, are more efficient in inhibiting the replication of the influenza virus than the corresponding single-stranded RNA fragments. The most effective nanocomplex that contained siRNA targeted at the chosen region of mRNA segment 5 of the viral genome reduced virus replication in the culture by a factor of 630. We have shown that non-agglomerated and water-soluble aminopropylsilanol nanoparticles are low-toxic, capable of delivering siRNA into cells and protecting siRNA in the Si~NH2/siRNA nanocomplexes from hydrolysis by cellular nucleases. Conclusion. The biological activity of the created nanocomplexes has been demonstrated by the example of highly effective selective suppression of influenza A/chicken/Kurgan/05/2005 virus replication in the cellular system.

Titanium dioxide or aminopropylsilanol nanoparticles were shown to be effective vehicles for delivering oligodeoxyribonucleotides and deoxyribozymes to cells to affect target nucleic acids. In this paper, the proposed principle of the delivery has been implemented in relation to oligoribonucleotides (ORN), components of short interfering RNAs (siRNAs). It has been shown that the obtained ORN-containing nanocomplexes (Si~NH2 ⋅ ORN) based on aminopropylsilanol nanoparticles penetrate eukaryotic cells. These nanocomplexes have been investigated as agents for suppressing the replication of influenza A virus (IAV) in the cellular system. It has been shown that the ORN strands targeted to (+)RNA and (-)RNA of the IAV 5th segment reduces the titer of the virus by 99.7% and 98.4%, respectively. Thus, oligoribonucleotides in the Si~NH2 ⋅ ORN nanocomplexes effectively inhibit the replication of the influenza A virus.

Background. To date, virologists have identified more than 25,000 influenza virus А serotypes, and their number will increase in the future. Therefore, the development of new antiviral drugs will always be relevant.The aim of the study is to obtain and test the chemical composition and antiviral activity of the lichen Cetraria islandica extracts against the influenza A virus.Material and methods. Samples of lichen Cetraria islandica (aqueous and ethanol extracts) were tested for toxic properties and antiviral activity against influenza A virus in MDCK cell culture.Results. Samples of aqueous and ethanol extracts of Cetraria islandica were obtained; their chemical composition was described. In MDCK cell culture, the extracts exhibited antiviral activity against human influenza virus А/H3N2 and avian influenza virus А/H5N1. When studying the mechanism of action of Cetraria islandica extracts, it was noted that Cetraria islandica samples possess pronounced antiviral properties against avian influenza A/chicken/Kurgan/05/2005 (H5N1) and human influenza A/Aichi/2/68 (H3N2) at the stage of their adsorption and reproduction.Conclusions. Samples of Cetraria islandica have antiviral activity at the stage of adsorption and reproduction of influenza A virus in MDCK cell culture. The ethanol extract shows a higher antiviral efficacy compared to the aqueous extract.

Rosa majalis Herrm. (Rosaceae) is a shrub widespread throughout Eurasia. In West Siberia, it is cultivated as an ornamental plant and raw material for the manufacture of fruit multivitamin concentrates. Meanwhile, metabolites and biological activities of its roots are poorly studied. The aim of this investigation was to evaluate the potential of ethyl acetate (EtOAc), butanol (ButOH), aqueous ethanol (EtOH), and aqueous (H 2 O) extracts of R. majalis roots as sources of antioxidant and anti-influenza compounds. Spectrophotometry and HPLC were used for metabolite quantification. Antioxidant activities were determined via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The antiviral activities were assessed as half-maximal inhibitory concentrations (IC 50 ). The EtOAc extract manifested the highest concentrations of phenolic compounds (53.79 mg g −1 of dry extract) and saponins (48.92 mg g −1 ). Total gallic acid was the main phenolic compound in all extracts (24.98–38.68 mg g −1 ). Catechin, free ellagic acid, and total ellagic acid had the highest levels in the EtOAc, H 2 O, and EtOH extracts, respectively (30.83, 22.38, and 34.95 mg g −1 ). The EtOAc extract showed the highest free-radical scavenging activity (2.31 trolox equivalents) and anti-influenza effects (IC 50 61.8 and 50.3 µg mL −1 ) against A/Aichi/2/68 (H3N2) and A/Chicken/05/2005 (H5N1), respectively. Our findings indicate good potential of these extracts for drug design against free-radical damage and influenza virus.

Introduction. Influenza A virus is the cause of epidemics and pandemics that severely affect the health and socioeconomic status of the world's population. The need to develop new methods of etiotropic therapy, and the increasing ability of viruses to counteract the antiviral drugs makes extremely relevant the search for new pharmacologically active substances and the subsequent study of their medicinal properties. The aim of the study is to conduct research into the antiviral properties of melanin obtained from the pharmaceutical chaga mushroom in relation to different subtypes of the influenza A virus. Materials and methods. A sample of water-soluble melanin from Inonotus obliquus obtained by alkaline hydrolysis and dried at 40C was tested for toxicity and antiviral activity. The commercial anti-influenza drug Tamiflu was used as a reference drug. Statistical processing of the obtained data was carried out according to the Spearman-Kerber method. Results. Inonotus obliquus melanin (sample 20-24) toxicity markers, such as a maximum tolerable concentration (MTC) of 237.0 g/mL, and a 50% cytotoxic concentration (CC50) of 153,45 g/mL were established for MDCK cell culture. The assessment of antiviral activity of test sample against three subtypes of the influenza A virus (H5N1, H3N2 and H1N1pdm09) demonstrated a decrease in the infectivity of the influenza virus by 2.53.5 lg with 50% virus-inhibiting concentrations (IC50) of 1.559.52 g/mL. Based on the obtained values of CC50 and IC50, the selectivity indices (SI) of the sample were calculated, characterizing its prospects for further research. Conclusions. Melanin obtained from the pharmaceutical chaga mushroom showed the highest activity against the strain of the human pandemic influenza virus A/California/04/2009 (H1N1)pdm09, caused a decrease in its infectivity by 3.5 lg and had an IC50 of 1.6 g/ml. The obtained results indicate the prospects for creating an antiviral drug based on Inonotus obliquus melanins against the influenza virus.

Dry ethanolic and aqueous extracts from fruiting bodies and cultivated mycelium of basidiomycetes were obtained and investigated for chemical composition. In vitro extracts are active against influenza virus A, herpes simplex virus type 2, vaccinia virus and mouse poxvirus. The in vivo antiviral activity of Fomes fomentarius mycelium extract against influenza virus subtype H3N2 was studied.

To optimize protocol for obtaining hairy roots of Nitraria schoberi L. with high antiviral activities, factors such as four strain types of Agrobacterium rhizogenes (A4, ATCC15834, R-1601, 8196), two explant types, namely cotyledonous and primary leaves of seedlings, and different cultivation durations (30 and 90 d) were studied. The formation of hairy roots was observed after 2 to 4 wk of incubation, depending on the type of explant and the strain of A. rhizogenes used. The maximum transformation frequency (85.7%) was observed in the cotyledons genetically modified with the strain ATCC15834. The transgenic nature of hairy roots was revealed by PCR with primers to the Agrobacterium oncogenes rolB and rolC. The absence of contamination of the culture by A. rhizogenes was confirmed by primers to the virC and virD1 genes. Phytochemical analysis showed that accumulation of individual metabolites in the line samples exceeded their levels in the native Nitraria roots. Catechin content in the cultures of long-term cultivation (90 d) was found 1.4 to 2.2 times higher than the same samples of short cultivation (30 d) and 4.8 to 10.8 times higher in comparison with the native roots. The most productive in terms of catechin level were hairy roots of long-term cultivation obtained during the transformation of primary leaves of N. schoberi seedlings with ATCC15834 strain. These data were consistent with the highest antiviral activities against influenza viruses of A (H5N1) and A (H3N2) subtypes with neutralization indexes 6.5 to 6.75 log10, and selectivity index values were in the range 15.4 to 16.4.

Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. Methods: The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. Results: The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Conclusion: Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments.

This is a study on antiviral activity of various extracts from the plant Monarda fistulosa L. cultivated in the forest-steppe zone of Western Siberia during the vegetation period. The activity of aqueous and aqueous-ethanolic extracts of M. fistulosa during the whole vegetation period and two polyphenolic fractions from this plant at the flowering stage was investigated against human influenza virus A/Aichi/2/68 (H3N2) and avian influenza virus A/chicken/Kurgan/05/2005 (H5N1). The anti-influenza activity was compared among the extracts and the polyphenolic fractions from M. fistulosa at the flowering stage. It was shown that antiviral activity against each subtype of the influenza A virus differed throughout the entire vegetation period, depending on the developmental stage of M. fistulosa and the type of extraction. Influenza virus A/Aichi/2/68 (H3N2) infectivity was most strongly inhibited by aqueous-ethanolic extracts from M. fistulosa raw material collected at the growth stage and by the aqueous extract from the fruiting initiation stage. Inhibition of the infectivity of influenza virus A/chicken/Kurgan/05/2005 (H5N1) was achieved by one or another M. fistulosa extract almost throughout the whole vegetation period. It is found that Polyphenolic Fractions 1 and 2 are more active against influenza virus A/Aichi/2/68 (H3N2), but aqueous and aqueous-ethanolic extracts are more active against influenza virus A/chicken/Kurgan/05/2005 (H5N1). On the condition of further in-depth studies, our experimental data suggest that M. fistulosa plant components can be recommended as medicinal (antiviral) substances against influenza viruses A/Aichi/2/68 (H3N2) and A/chicken/Kurgan/05/2005 (H5N1).

The antiviral activity of the experimental preparation based on catechins and leucoanthocyanins of Alchemilla vulgaris was studied in experiments on outbred ICR mice against influenza A/H3N2 and A/H5N1 viruses. 50 % effective doses of the Alchemilla vulgaris preparation against these subtypes were calculated, amounting 14.1 and 31.6 μg/g of mouse weight, respectively. It was found that the sample in dose 25 μg/g of weight protects mice from death by 60 and 64 % compared to the corresponding virus control.

The toxicity and antiviral activity of extracts obtained by the methods of aqueous and ethanol extraction of bioactive substances from Cetraria islandica lichen as a raw material were studied. Aqueous and ethanol extracts of lichen were characterized by low toxicity with respect to the passaged MDCK cell culture and exhibited antiviral activity. The ethanol extract showed more potent in vitro antiviral activity against human A/H3N2 and avian A/H5N1 influenza viruses: in a concentration of 50 μg/ml, it suppressed replication of these viruses by 3.5 and 4 log10, respectively, while the aqueous extract inhibited replication of viruses by 2 and 6 log10, respectively, when taken in a concentration of 500 μg/ml that was 10-fold higher than the concentration of the ethanol extract.

The rapid emergence of influenza virus A resistance to current antivirus drugs has raised an urgent need for developing safe and effective remedies based on plants. Hairy roots are considered an efficient system for the large-scale production of valuable compounds with potent antiviral activity. We have evaluated for the first time an antivirus activity in Astragalus penduliflorus Lam. hairy roots (APHRs) lines obtained from cotyledons (APHR 2), primary shoots (APHR 5), and hypocotyls (APHR 6) against influenza A/Aichi/2/68 (H3N2) and A/chicken/Kurgan/05/2005 (H5N1) subtypes. Estimation of the antiviral activity was based on the analysis of cytotoxic activity, selectivity and neutralization indexes. All tested samples demonstrated low toxicity for MDCK cell culture corresponding to the modern requirement for antiviral drugs. Index neutralization (IN) was 2.50 in APHR 2, 28 d extract against H3N2 subtype, whereas the highest IN against H5N1 (2.25) was detected for line APHR 5 56 d The levels of selectivity index observed in APHR 5, and APHR 6 were higher in comparison with APHR 2, corresponding to the level of antioxidants, determined by the DPPH radical scavenging assay and total antioxidant activities by amperometric method. Major phenolic compounds identified in APHRs lines extracts by HPLC analysis, including flavonoids, hydroxybenzoic, hydroxicinnamic acids, could be responsible for the antiviral activities. (c) 2022 SAAB. Published by Elsevier B.V. All rights reserved.

In this work, it was revealed that water and ethanol extracts of the plants Nepeta cataria, Nepeta sibirica, Scutellaria baicalensis, Hyssopus officinalis, Betonica officinalis, and water extracts of Dracocephalum moldavica, Glechoma hederacea, Mentha arvensis, Prunella vulgaris, Melissa officinalis ethanol extracts of Mentha piperita, Mentha crispa, Origanum vulgare, Hyssopus officinalis, Salvia verticillata showed antiviral activity against the influenza virus subtype H5N1. Aqueous extracts of Nepeta cataria and Glechoma hederacea (NI 3.75) showed the highest antiviral effect against the H5N1 subtype. It was revealed the antiviral activity against influenza virus subtype H3N2 of aqueous and ethanol extracts of Scutellaria baicalensis, Mentha piperita, Mentha arvensis, Mentha crispa, aqueous extract of Dracocephalum moldavica and ethanol extracts of Glechoma hederacea, Origanum vulgare, Prunella vulgaris, Hyssopus officinalis, Betonica officinalis, Salvia verticillata. Ethanolic extract of Betonica officinalis (NI 4.25) showed the highest virus neutralizing activity against the H3N2 subtype. It was carried out chemical analysis of the aerial parts of plants of the Lamiaceae family. It was shown that the highest content of flavonols was observed in Dracocephalum nutans (4.47±0.04%), the highest content of tannins was found in Mentha arvensis (17.62 ± 0.78%), and the highest content catechins were found in Nepeta cataria (0.43 ± 0.007%). Thus, plant extracts of the Lamiaceae family are promising sources for further studies to develop new antiviral drugs.

Изучена фармакокинетика субстанции нового противооспенного препарата НИОХ-14 (аналога разработанного в США соединения ST-246) у мышей после однократного перорального введения в дозе 50 мкг/г и перорального введения в течение 10 сут в дозах 50 и 5 мкг/г. Концентрацию активного метаболита (то есть ST-246), в который НИОХ-14 превращается в сыворотке крови и гомогенатах органов мышей, определяли методом LC-MS/MS (тандемной масс-спектрометрии — MS/MS и жидкостной хроматографии — LC). На основании фармакокинетических параметров была определена тканевая доступность субстанции НИОХ-14 для разных органов мыши, которая составила 100; 69,6; 20,3; 26,8 и 63,3 % для легких, печени, селезенки, головного мозга и почек, соответственно.